Some degree of incontinence from mild dribbling to severe intermittent urine loss is seen in one out of ten people over the age of 65. The causes of this defect in many circumstances can be well defined where nerve lesions in the spinal cord or bladder outlet occur. There are, however, a large segment of the population who have idiopathic incontinence and within this group are a large number of patients that exhibit apparent neuromascular defects since other factors appear normal. Since this defect in the physiological control of the lower urinary tract may be mediated by an imbalance in the component of the neurotransmission events, that of the receptors for neurotransmitters. Employing radioligand binding techniques, it is now possible to accurately measure receptor binding on in vitro bladder smooth muscle samples for a number of neurotransmitter substances. The initial studies will center on three autonomic receptors; muscarinic, using (3H)QNB, Alpha-adrenergic, using (3H) dihydroergocryptine and Beta-adrenergic receptors using 125 iodocyanopindolol on bladder smooth muscle homogenates. Longer term goals will permit measurements of; nicotinic, histamine, peptide receptors and selective Alpha1 and Alpha2 receptor ligands. Early experiments to perfect protocols for each ligand will be studied on the rabbit bladder and then applied to human tissue obtained from surgical specimens and autopsy tissue segments. Emphasis will be placed on establishing normal receptor populations in four age groups: children, young and middle aged adults and age 65 years or more. These normal groups will then serve to compare tissues obtained from individuals with micturition defects, especially incontinence with individuals over 65 years. The information learned from receptor binding experiments will be useful in assessing changes in autonomic control of the urinary related to increases or decreases in bladder responsiveness because of changes in the density (B max) or affinity (KD) of the various receptor populations associated with aging. It will also be possible to describe local pathophysiologic changes that may occur associated with incontinence and other pathologic conditions resulting in bladder dysfunction especially in that group of patients with no other apparent neurologic defect.